It is known that liver cirrhosis patients often have protein-energy malnutrition (PEM). Protein malnutrition has been evaluated based on serum albumin value. When the value is 3.5 g/dl or less, the subject is determined to be in a protein malnutrition state (Non-patent Document 1). Further, energy malnutrition is evaluated based on the respiratory quotient obtained from indirect calorimetry. When the value (non-protein respiratory quotient) is less than 0.85, the subject is determined to be in an energy malnutrition state. It is reported that 70% of liver cirrhosis patients are in a protein malnutrition state, 62% of them are in an energy malnutrition state, and 50% of them have a combined symptom of protein malnutrition and energy malnutrition (i.e., PEM).
Of these patients with malnutrition, liver cirrhosis patients in an energy malnutrition state are known to fall into a kind of starvation state, even if they have ordinary meals. This particularly occurs when there is a long interval between the meals. This type of phenomenon typically occurs at night, i.e., due to the long interval between dinner and breakfast the next day. It is said that liver cirrhosis patients may fall into a starvation state, even within one night, to an extent equivalent to that of a healthy subject who has fasted for three days. Since energy malnutrition greatly influences prognosis or quality of life, it is important to perform an appropriate diet therapy to alleviate the starvation state. For example, a common technique has been late-evening snacking (LES), in which the patients have a small amount of meal before bedtime so as to avoid energy shortage in the liver at night (Non-patent Document 2).
On the other hand, such diet therapies, in particular, late-evening snacking, increase meal frequency; moreover, since late-evening snacking allows the patients to have a meal before bedtime, there is a risk of obesity due to extra calories. Further, particularly for patients with diabetes, borderline diabetes, insulin resistance, obesity, or the like, it is desirable to consider performing late-evening snacking or similar treatments in consideration of these diseases. Therefore, in diet therapy for liver cirrhosis patients, it is desirable to understand the presence or absence of the energy malnutrition state of the liver cirrhosis patients, while also considering the presence or absence of other diseases such as diabetes, borderline diabetes, insulin resistance, and the like.
As described above, energy malnutrition has previously been evaluated using, as an index, the respiratory quotient obtained from indirect calorimetry. In this method, the metabolic states of the nutrient factors in the body have been indirectly evaluated using a volume ratio of carbon dioxide excretion amount to oxygen consumption amount upon energy conversion. However, indirect calorimetry is expensive, requires a special device, and is only performed in limited institution. Therefore, currently, indirect calorimetry is applied to only a limited number of patients. Further, to ensure accurate measurement and calculation of the respiratory quotient, the measurement of indirect calorimetry usually takes at least two hours. During the measurement, the patients must be kept quiet in bed, and prevented from falling asleep. Therefore, in order to ensure that the measurement is performed under appropriate conditions, monitoring by an observer or the like is necessary. This causes pain to and burdens both the patient and the observer. Further, as described above, since the evaluation by indirect calorimetry is indirect evaluation based on the respiratory quotient determined by calculation, it is unclear what nutrient factor actually combusted. If the presence or absence, or the extent of the energy malnutrition state is unclear, it is difficult to perform an appropriately diet therapy. Further, in the case where execution of diet therapy for an energy malnutrition state must be determined in consideration of the presence or absence of other diseases such as diabetes, if the evaluation of energy malnutrition is difficult and troublesome, it may further hinder an appropriate treatment. Moreover, prolonged multiple tests increase the burden of the patient.
Therefore, it is important to easily and rapidly determine an energy malnutrition state of a liver disease subject, for example, a liver cirrhosis patient and a liver disease subject having a pre-liver cirrhosis condition, such as non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). It is also important to perform an appropriate diet therapy in consideration of the presence or absence of other diseases, such as diabetes, borderline diabetes, insulin resistance and the like.